Scottish deer forests are mainly a Highland phenomenon. Many were formed during the nineteenth century when proprietors benefited from their economic marketability as 'sporting estates'. The Blackmount area was a forest, under the ownership of the Campbells of Glenorchy, since the fifteenth century. Situated in one of the most mountainous ranges of the west Highlands, its function was to serve as a hunting reserve for both that family and their aristocratic peers, whilst being protected by foresters from poachers and trespassers. The earlier Forest of Corrie Ba ceased to exist during the later eighteenth century when sheep farming became the predominant land use there. Blackmount Forest was re-formed anew in 1820 due to an economic recession after the Napoleonic Wars terminated. This thesis identifies the social, political, economic, geographical and environmental reasons for Blackmount Forest's creation, growth and continued existence. It questions if this was for leisure alone or for a commercial ethos adopted by landlords of other forests. The Forest expanded during the nineteenth century, gaining national recognition, especially in the 1840s-1850s and thereafter. However, the Campbells of Breadalbane faced internal and external challenges and criticisms, several of a legal nature. The family were long established, in the Scottish aristocracy, with extensive estates in the west-central Highlands. The retained Blackmount for themselves, excepting the period 1863-1885 when it was let out wholesale. The thesis also identifies its social impact upon the locality, and the extent to which this forest may have influenced others coming into existence later that century.

Resistance to chemotherapeutics is a widespread phenomenon in cancer cells that may counteract the successful therapy of many patients. In resistant cells, higher level of ABC transporters, among others, often can be detected. This high level of ABC transporters represents a suspected mechanism of acquired cancer resistance. We studied the molecular mechanism of resistance to taxanes in cancer cells using SK-BR-3 and MCF-7 breast cancer cell lines. We analyzed the effect of paclitaxel on apoptosis induction in the originally sensitive cells of these lines as compared to their counterpart resistant cells, developed by gradual adaptation to paclitaxel. In resistant cells of the SK-BR-3 and MCF-7 lines, we did not detected ongoing induction of apoptosis but we did detect significantly increased expression of ABCB1 transporter after paclitaxel application. By silencing the expression of the transport via employment of small interfering RNA (siRNA), we tested the role of the ABCB1 transporter in cells resistant to paclitaxel. We found that resistant cells with silenced expression of the ABCB1 transporter had a statistically significant increase of sensitivity to paclitaxel as compared to control resistant cells with high expression of this transporter. Along with increased sensitivity, we demonstrated...

John Lott berechnete eine Signatur mit ganzzahligen Werten für den Orbitraum einer kompakten, orientierbaren (4k + 1)-Mannigfaltigkeit mit einer halbfreien S1-Wirkung. Diese Signatur ist eine Homotopieinvariante für den Orbitraum. Allerdings konstruierte er keinen Operator vom Dirac-Typ, der die Signatur als Index besitzt. In dieser Arbeit konstruieren wir einen solchen Operator auf dem Orbitraum der S1-Wirkung, einem Thom-Mather stratifizierten Raum mit einem singulären Stratum von positiver Dimension, und wir zeigen, dass der Operator im wesentlichen eindeutig bestimmt ist. Ferner zeigen wir, dass sein Index mit Lotts Signatur übereinstimmt, zumindest wenn der stratifizierte Raum die sogenannte Witt-Bedingung erfüllt. Wirnennendiesen Operator den induzierten Dirac-Schrödinger Operator. Unsere Konstruktionsstrategie ist es, einen geeigneten S1-invarianten transversal elliptischen Operator erster Ordnung auf den S1-invarianten Differentialformen zu definieren, der den gesuchten Operator auf den Differentialformen des Orbitraums induziert. Die Witt-Bedingung, eine topologische Bedingung, welche in diesem Fall von der Kodimension der betrachteten Punktmenge abhängt, lässt verschiedene analytische Schlussfolgerungen zu. Insbesondere ist, wenn die Bedingung nicht erfüllt ist, der Hodge-de Rham Operator auf dem Quotientenraum nicht notwendigerweise essentiell selbstadjungiert und die Wahl einer Randbedingung ist daher notwendig. Diese Wahlfreiheit erscheint unnatürlich in Anbetracht der Tatsache, dass Lotts Signatur unabhängig von der Witt-Bedingung wohldefiniert ist. Der Dirac-Schrödinger Operator, der in dieser Arbeit konstruiert wird, unterschei- det sich vom Hodge-de Rham Operator durch einen Term nullter Ordnung, welcher sicherstellt, dass der Operator wesentlich selbstadjungiert ist. Außerdem antikommutiert dieser Term nullter Ordnung mit der Signatur-Involution, wodurch der gesamte Operator zerfällt und so der Index berechnet werden kann, auch wenn die Witt-Bedingung nicht erfüllt ist. / John Lott has computed an integer-valued signature for the orbit space of a compact orientable (4k + 1) manifold with a semi-free S1-action, which is a homotopy invariant of that space, but he did not construct a Dirac type operator which has this signature as its index. In this Thesis, we construct such operator on the orbit space, a Thom-Mather stratified space with one singular stratum of positive dimension, and we show that it is essentially unique and that its index coincides with Lott’s signature, at least when the stratified space satisfies the so called Witt condition. We call this operator the induced Dirac-Schrödinger operator. The strategy of the construction is to “push down” an appropriate S1-invariant first order transversally elliptic operator to the quotient space. The Witt condition, a topological condition which in this case depends on the codi- mension of the fixed point set, has various analytic consequences. In particular, when not satisfied, the Hodge-de Rham operator on the quotient space does not need to be essentially self-adjoint and therefore a choice of boundary conditions is required. This choice freedom is not natural in view of the fact that Lott’s signature is well defined independently of the Witt condition. The Dirac-Schrödinger operator constructed in this Thesis differs from the Hodge-de Rham operator by a zero order term which ensures it to be essentially self-adjoint. Moreover, this zero order term anti-commutes with the chirality involution allowing the whole operator to split so that the index can be computed even if the Witt condition is not satisfied.

Wir betrachten ein System nichtlinearer parabolischer partieller Differentialgleichungen zur Modellierung des biologischen Phänomens Chemotaxis, das unter anderem in Aggregationsprozessen in Lebenszyklen bestimmter Einzeller eine wichtige Rolle spielt. Unser Chemotaxismodell benutzt Sensitivitäts funktionen, die die vorkommenden biologischen Prozesse genauer spezifizieren. Trotz der durch die Sensitivitätsfunktionen eingebrachten, zusätzlichen Nichtlinearitäten in den Gleichungen erhalten wir zeitlich globale Existenz von Lösungen für verschiedene biologisch realistische Klassen von Sensitivitätsfunktionen und können unter unterschiedlichen Bedingungen an die Systemdaten Konvergenz der Lösungen zu trivialen und nicht-trivialen stationären Punkten beweisen. / We consider a system of non-linear parabolic partial differential equations modeling chemotaxis, a biological phenomenon which plays a crucial role in aggregation processes in the life cycle of certain unicellular organisms. Our chemotaxis model introduces sensitivity functions which help describe the biological processes more accurately. In spite of the additional non-linearities introduced by the sensitivity functions into the equations, we obtain global existence of solutions for different classes of biologically realistic sensitivity functions and can prove convergence of the solutions to trivial and non-trivial steady states.

In der vorliegenden Arbeit "Nichtkommutative Blochtheorie" beschäftigen wir uns mit der Spektraltheorie bestimmter Klassen von Hilbertraumoperatoren, den elliptischen Operatoren auf Darstellungsräumen von Hilbert-C*-Moduln. Die auftretenden C*-Algebren kodieren dabei Symmetrieeigenschaften der entsprechenden Operatoren.Für kommutative Symmetrien ist die Blochtheorie ein geeignetes Hilfsmittel. Wir schildern diese Methode zunächst in einem geometrischen Kontext, der allgemein genug ist, um die bekannten Ergebnisse über die Abwesenheit singulärstetigen Spektrums im Hinblick auf physikalische Anwendungen zu erweitern. Wir lassen uns dann durch eine Neuinterpretation der Blochtheorie aus einem nichtkommutativen Blickwinkel inspirieren zur Entwicklung einer nichtkommutativen Blochtheorie. Dabei werden bestimmte Eigenschaften von C*-Algebren verknüpft mit Eigenschaften des Spektrums elliptischer Operatoren. Diese Blochtheorie für Hilbert-C*-Moduln erlaubt es, verschiedene bekannte Resultate aus dem Bereich kommutativer (diskreter und kontinuierlicher) Geometrien mit nichtkommutativen Symmetrien in einem neuen gemeinsamen Rahmen zusammenzufassen, der Raum läßt für Modelle nichtkommutativer Geometrien mit nichtkommutativen Symmetrien. Wichtigstes Beispiel für die behandelte Klasse von Operatoren in der mathematischen Physik sind die Schrödingeroperatoren mit periodischem Magnetfeld und Potential. Wir ordnen sie in den Rahmen kommutativer und nichtkommutativer Blochtheorie ein und wenden die zuvor bereitgestellten Methoden an. / In this doctoral thesis "Nichtkommutative Blochtheorie'' (non-commutative Bloch theory) we investigate the spectral theory of a certain class of operators on Hilbert space: the elliptic operators associated with representations of Hilbert C*-modules. The C*-algebras that arise encode symmetry properties of the corresponding operators. For commutative symmetries Bloch theory is a proper tool. We describe this method in a geometric context which is general enough to extend known results about absence of singular continuous spectrum in view of physical applications. Then --- inspired by a new interpretation of Bloch theory from a non-commutative point of view --- we develop a non-commutative Bloch theory. Here certain properties of C*-algebras get linked to spectral properties of elliptic operators. This Bloch theory for Hilbert \CS-modules allows to unite, in a new common framework, several known results from the field of commutative (discrete and continuous) geometries having non-commutative symmetries; this leaves ample room for models of non-commutative geometries having non-commutative symmetries. In mathematical physics, the most important example for the class of operators considered is given by the Schrödinger operators with periodic magnetic field and potential. We place them into the framework of commutative and non-commutative Bloch theory and apply the methods developed before.

In der Ramsey Theorie fuer Graphen haben Burr und Erdos vor nunmehr fast dreissig Jahren zwei Vermutungen formuliert, die sich als richtungsweisend erwiesen haben. Es geht darum diejenigen Graphen zu charakterisieren, deren Ramsey Zahlen linear in der Anzahl der Knoten wachsen. Diese Vermutungen besagen, dass Ramsey Zahlen linear fuer alle degenerierten Graphen wachsen und dass die Ramsey Zahlen von Wuerfeln linear wachsen. Ein Ziel dieser Dissertation ist es, abgeschwaechte Varianten dieser Vermutungen zu beweisen. In der topologischen Ramseytheorie bewies Kojman vor kurzem eine topologische Umkehrung des Satzes von Hindman und fuehrte gleichzeitig sogenannte Hindman-Raeume und van der Waerden-Raeume ein (beide sind eine Teilmenge der folgenkompakten Raeume), die jeweils zum Satz von Hindman beziehungsweise zum Satz von van der Waerden korrespondieren. In der Dissertation wird zum einen eine Verstaerkung der Umkehrung des Satzes von van der Waerden bewiesen. Weiterhin wird der Begriff der Differentialkompaktheit eingefuehrt, der sich in diesem Zusammenhang ergibt und der eng mit Hindman-Raeumen verknuepft ist. Dabei wird auch die Beziehung zwischen Differentialkompaktheit und anderen topologischen Raeumen untersucht. Im letzten Abschnitt des zweiten Teils werden kompakte dynamische Systeme verwendet, um ein klassisches Ramsey-Ergebnis von Brown und Hindman et al. ueber stueckweise syndetische Mengen ueber natuerlichen Zahlen und diskreten Halbgruppen auf lokal zusammenhaengende Halbgruppen zu verallgemeinern. / In graph Ramsey theory, Burr and Erdos in 1970s posed two conjectures which may be considered as initial steps toward the problem of characterizing the set of graphs for which Ramsey numbers grow linearly in their orders. One conjecture is that Ramsey numbers grow linearly for all degenerate graphs and the other is that Ramsey numbers grow linearly for cubes. Though unable to settle these two conjectures, we have contributed many weaker versions that support the likely truth of the first conjecture and obtained a polynomial upper bound for the Ramsey numbers of cubes that considerably improves all previous bounds and comes close to the linear bound in the second conjecture. In topological Ramsey theory, Kojman recently observed a topological converse of Hindman's theorem and then introduced the so-called Hindman space and van der Waerden space (both of which are stronger than sequentially compact spaces) corresponding respectively to Hindman's theorem and van der Waerden's theorem. In this thesis, we will strengthen the topological converse of Hindman's theorem by using canonical Ramsey theorem, and introduce differential compactness that arises naturally in this context and study its relations to other spaces as well. Also by using compact dynamical systems, we will extend a classical Ramsey type theorem of Brown and Hindman et al on piecewise syndetic sets from natural numbers and discrete semigroups to locally connected semigroups.

The functions of the immune system include immunosurveillance of transformed cells, i.e., the ability to eliminate these cells before they become harmful to the organism. If the transformed cells succeed to escape the immune system surveillance, an oncological disease develops. The tumour immunotherapy aims to stimulate the immune system mechanisms to fight against the tumour. Lately, there's an interest in using NK cells in the immunotherapy of tumours. These cells appertain to the innate immune system and participate in immunosurveillance. When an NK cell encounters a target cell, its activation depends on the integration of signals from the surface activating and inhibiting receptors which bind ligands on the surface of the target cell. Upon activation, NK cell exhibits a cytotoxic response against the target cell. The use of NK cells in immunotherapy includes, among others, the testing of bispecific fusion proteins which can bind a tumour surface antigen by one part and NK cell activating receptor by the other part. Thus, these fusion proteins mediate a contact between both cells and trigger the cytotoxic response. This work presents a preparation of bispecific fusion proteins which consist of an activating ligand MICA (for the receptor NKG2D) or B7H6 (for the receptor NKp30), and a nanobody...

Herpes simplex virus (HSV) infection of the cornea leads to a blinding immuno-inflammatory condition of the eye also called stromal keratitis (SK). SK immunopathology is characterized by the infiltration of CD4+ T cells of Th1 phenotype as well as the development of new blood vessels into the normally avascular cornea. Studies in mouse models of SK have firmly established the role of CD4+ T cells, and particularly of Th1 phenotype, as the principal mediators of SK immunopathology. However, with the recent discovery of IL-17A and Th17 cells, the role of this cytokine as well as Th17 cells remains to be further defined. Recently it was shown that the normal cornea expresses VEGF-A, however its biological activity is impeded by its binding to a soluble form of VEGF-A receptor-1 (sVEGFR-1). Past studies have implicated the role of vascular endothelial growth factor-A (VEGF-A) in HSV induced corneal angiogenesis, however the source of VEGF-A as well as molecular mechanisms, particularly in the context of VEGF-A/sVEGFR-1 balance during HSV infection, are poorly understood. The first part of this dissertation (I) reviews past literature on HSV induced corneal SK immunopathology. It focuses on the understanding of HSV-1 induced events that particularly results in corneal angiogenesis as well as tissue damage mediated by different type of cells as well as their secreted products. The next three parts (II-IV) focus on the mechanisms of HSV induced corneal angiogenesis as well as the relative role of Th1 and Th17 cells in SK immunopathology. Results in part II focuses on the relative role of IFN-γ/IL-17 as well as Th1/Th17 cells in HSV induced corneal immunopathology. The third section evaluate the significance of VEGF-A/sVEGFR-1 balance in HSV induced corneal neovascularization. Results in part IV focus on the role of IL-17A in altering the balance between VEGF-A and sVEGFR-1 post ocular HSV infection and subsequent corneal angiogenesis. Collectively these studies identified novel mechanisms by which HSV infection of the cornea leads to the development of angiogenesis as well as corneal tissue damage and subsequent SK immunopathology, the most common cause of infectious blindness in the Western World.

The enzyme phospholipase A2 (PLA2) specifically hydrolyzes the 2-acyl ester bond of 1,2-diacyl-3-sn-phosphoglycerides releasing fatty acids and lysophospholipids in the presence of Ca2+. Both products represent precursors for signaling molecules that can exert a multitude of biological functions including phospholipid metabolism, exocytosis and inflammation. Consequently, PLA2 not only plays a role in regulating physiological processes, but also exhibits pharmacological effects in inflammatory diseases. Nevertheless, the signaling pathway leading to cell death still remains elusive. In the present study, the cytotoxicity of Naja naja atra PLA2 toward human neuroblastoma SK-N-SH cells and leukemia K562 cells were respectively evaluated to explore the signaling pathway of PLA2-induced cell death. Upon exposure to PLA2, p38 mitogen-activated protein kinase (p38 MAPK) or c-Jun N-terminal kinase (JNK) activation, extracellularsignal-regulated protein kinase (ERK) inactivation, reactive oxygen species (ROS) generation, increase in intracellular Ca2+ concentration, the loss of mitochondrial membrane potential (£G£Zm), cytochrome c release and upregulation of Fas/FasL were found in SK-N-SH or K562 cells. N-Acetylcysteine (ROS scavenger), BAPTA-AM (Ca2+ chelator), SB202190 (p38 MAPK inhibitor) or SP600125 (JNK inhibitor) abrogated p38 MAPK or JNK activation and rescued cell viability, £G£Zm, cytochrome c release and suppressed Fas/FasL upregulation of PLA2-treated cells, but restored phosphorylation of ERK. Activated ERK was found to attenuate p38 MAPK-mediated upregulation of Fas/FasL. Besides, sustained JNK activation was also observed in SB202190/PLA2-treated K562 cells after exterminating p38 MAPK activation, but also retained the cytotoxicity of PLA2. Knockdown of p38 MAPK or JNK1 by siRNA proved that PLA2 induced Fas/FasL upregulation through p38 MAPK/ATF-2 or JNK1/c-Jun pathways in K562 cells. Furthermore, deprivation of catalytic activity could not diminish PLA2-induced cell death and Fas/FasL upregulation. The cytotoxicity of arachidonic acid (AA) and lysophosphatidylcholine (LPC) was not related to the expression of Fas/FasL. The results showed that the cytotoxicity of AA is mediated through mitochondria-dependent death pathway, eliciting by AA-induced ROS generation and Ca2+-evoked activation of p38 MAPK and JNK. Besides, ERK activation abrogated by U0126 improved the ability of AA-mediated Fas/FasL upregulation in K562 cells. Taken together, our results indicate that PLA2-induced cell death is through Ca2+- and ROS evoked p38 MAPK or JNK activation. Upregulation of Fas/FasL partially involves in cytotoxicity of PLA2.

This thesis presents a detailed study of life cycle greenhouse gas (GHG) emissions intensity during the uranium mining-milling phase of the nuclear fuel cycle for three paired uranium mine-mill operations in northern Saskatchewan (SK). The study period runs from 2006 – 2013 for two of the three pairs, and from 1995-2010 for the third. The life cycle analysis has been conducted based on the ISO 14040:2006 standard using a Process Chain Analysis methodology. This study differs from previous studies of GHG emissions intensity during the uranium mining-milling phase of the nuclear fuel cycle in two key respects. First, it has a very large system boundary which includes the uranium exploration and mine-mill decommissioning phases. Second, it utilizes a life cycle inventory database to include many processes which would normally fall outside of the system boundary due to their small individual contributions. These differences contribute to a more accurate result. The production-weighted average life cycle GHG emissions intensity is estimated as 45 kg CO2e/kg U3O8 at an average ore grade of 9.12% U3O8 based on relative U3O8 production volumes at Mine-Mill A, B, and C from 2006 to 2010. The 95% confidence interval for the production-weighted average result ranges from 42 to 49 kg CO2e/kg U3O8, indicating that overall uncertainty in the result is low. Life cycle GHG emission intensity for the three uranium mine-mill pairs are 84, 66, and 35 kg CO2e/kg U3O8 at average ore grades of 0.71%, 1.54%, and 11.5% U3O8 respectively. Nearly 90% of life cycle GHG emissions are associated with operation of the uranium mine-mills, primarily from energy consumption during operation (69% of total) transport of materials and personnel (7.0%), and use of reagents (5.6%). Remaining processes each individually account for less than 5% of the total. In calculating emissions from electricity consumption, the base-case emission intensities reported above use a province-wide electricity emission factor because the utility does not differentiate its emissions by region. However, the facilities included in this study are all located in Northern Saskatchewan, which is powered exclusively by hydropower. Application of a regional emission factor reduces the production-weighted average life cycle GHG emission intensity to 26 kg CO2e/kg U3O8 with a 95% confidence interval of 25 to 29 kg CO2e/kg U3O8. This represents a 42% reduction in life cycle GHG emission intensity from the base case. Due to the high uranium ore grades found in SK uranium deposits, life cycle GHG emissions intensity for uranium from SK is among the lowest in the world. Further, the life cycle GHG emission intensity estimate from uranium mining-milling in SK is a small (approximately 10%) contributor to the life cycle GHG emissions intensity from the nuclear fuel cycle for light water reactors overall, amounting to approximately 1.2 g CO2e/kWh electricity (0.6 g CO2e/kWh electricity calculated using the regional hydroelectric power source).